Studies are planned on the possible role of interferons (IFNS) in modu- lating the immune response in connective tissue diseases such as SLE and RA. Cellular origin, controlling mechanisms of production as well as influence on in vitro models of humoral and cell-meidated immunity will be examined with particular attention to acid-labile Alpha IFN (AL Alpha IFN) which is known to be elevated in SLE serum. AL Alpha IFN will be isolated by affinity columns composed of sepharose linked to anti-Alpha IFN anti- body. Comparison of AL Alpha IFN and non acid labile Alpha IFN will be made for their effects on Natural Killer cell function as well as in vitro B cell function and T cell activation. Possible direct participation of Alpha IFN in immune complex lesions of lupus glomerulonephritis will be studies in parallel with a wide variety of other chronic renal diseases. Renal and skin tissue deposition of Alpha IFN will be determined by indirect immunofluorescence and possible interactions between Alpha IFN and components of immune complexes or glomerular basement membrane measured. Synovial tissues from patients with rheumatoid arthritis will be studied for both a and Gamma IFN production and modulation of Gamma IFN release by prostaglandin E2 examined, using short-term synovial tissue cell cultures. The possibility that materials released from co-cultured synovial tissues may induce IFN production by peripheral blood mononuclear cells will be studied. In addition the role of endogenous factors such as anti-lympho- cyte antibodies, putative autoantigens (DNA, autologous aggregated IgG, nucleotides, or cucleic acids) in stimulating IFN release will be examined. An attempt will also be made to determine whether both Alpha IFN and Gamma IFN are produced in conjunction with any easily demonstrable immune control mechanisms. Finally Gamma IFN wil be studied for its demonstrable effect on in vitro T and B cell interaction.